Am J Pathol., 2006, Volume 169; Pages 1913 - 1924.

α-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters .

Fiaccavento, R. Carotenuto, F. Minieri, M. Masuelli, L. Vecchini, A. Bei, R. Modeesti, A.

Key Findings:

The UM-X7.1 hamster strain displays abnormal accumulation of n6 fatty acids in the heart and severely damaged cardiac mitochondrial and cellular membranes. The objective here was to modify the lipid composition of the hearts of cardiomyopathic hamsters (CMPHs) through an ALA enriched diet. ALA administration led to a significant elongation of the survival of hamsters suffering from hereditary cardiomyopathy. ALA showed protective effects on cardiac cells and on cardiac tissue structure and function against damage induced by gamma-SG ablation1and mitochondrial gene mutation. According to the authors, the beneficial findings in CMPH/FS hearts may be due to high ALA and EPA and the relatively low AA content. The effects of dietary ALA on cardiomyopathic hamsters culminated in a postponement of cardiac failure and an extension of longevity, with more than 60% of CMPH fed with flaxseeds alive and apparently in good health after all control CMPH/PT had perished. The data suggest that ALA can be used to prevent the cardiac damage of hereditary diseases.

ABSTRACT:

Randomized clinical trials have demonstrated that the increased intake of n3 polyunsaturated fatty acids significantly reduces the risk of ischemic cardiovascular disease, but no investigations have been performed in hereditary cardiomyopathies with diffusely damaged myocardium. In the present study, gamma sarcoglycan-null cardiomyopathic hamsters were fed from weaning to death with an alpha-linolenic acid (ALA) enriched versus standard diet. Results demonstrated a great accumulation of ALA and eicosapentaenoic acid and an increased eicosapentaenoic/arachidonic acid ratio in cardiomyopathic hamster hearts, correlating with the preservation of myocardial structure and function. In fact, ALA administration preserved plasmalemma and mitochondrial membrane integrity, thus maintaining proper cell/extracellular matrix contacts and signaling, as well as a normal gene expression profile (myosin heavy chain isoforms, atrial natriuretic peptide, transforming growth factor beta 1) and a limited extension of fibrotic areas within ALA-fed cardiomyopathic hearts. Consequently, hemodynamic indexes were safeguarded, and more than 60% of ALA fed animals were still alive (mean survival time, 293 +/- 141.8 days) when all those fed with standard diet were deceased (mean survival time, 175.9 +/- 56 days). Therefore, the clinically evident beneficial effects of n3polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis. (Authors abstract)

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